African Swine Fever (ASF)
African swine fever is a devastating haemorrhagic disease of domestic pigs caused by a double-stranded DNA virus, African swine fever virus (ASFV). ASFV is the only member of the Asfarviridae family and replicates predominantly in the cytoplasm of cells. Virulent strains of ASFV can kill domestic pigs within about 5-14 days of infection with a mortality rate approaching 100%.
ASFV can infect and replicate in warthogs (Phacochoerus sp.), bushpigs (Potamocherus sp.) and soft ticks of the Ornithodoros species, but in these species few if any clinical signs are observed and long term persistent infections can be established. The disease is currently endemic in many sub-Saharan countries and in Europe in Sardinia. Following its introduction to Georgia in the Trans Caucasus region in 2007, ASFV has spread extensively through neighbouring countries including the Russian Federation. In 2012 the first outbreak was reported in Ukraine and in 2013 the first outbreaks in Belarus. In 2014 further outbreaks were reported in pigs in Ukraine and detection in wild boar in Lithuania and Poland.
There is currently no treatment for ASF. Prevention in countries outside Africa has been attempted on a national basis by restrictions on incoming pigs and pork products, compulsory boiling of waste animal products under license before feeding to pigs and the application of a slaughter policy when the disease is diagnosed. Prevention in Africa is based on measures to keep warthogs and materials contaminated by warthogs away from the herd.
To date, no effective attenuated or inactivated vaccines have been developed.
There is thus a need for improved measures to control ASFV infection and prevent spread of the disease.
African Swine Fever Virus (ASFV)
The ASFV genome encodes five multigene families (MGF 100, MGF 110, MGF 360 and MGF 505/530) located within the left hand 35 kb or right hand 15 kb terminal variable regions. The MGFs constitute between 17 and 25% of the total coding capacity of the ASFV genome. They lack similarity to other known genes. Although the function of individual MGF genes is unknown, it has been shown the MGF 360 and 505 families encode genes essential for host range function that involves promotion of infected-cell survival and suppression of type I interferon response.
The OURT88/3 Isolate
OURT88/3 is a non-pathogenic isolate of ASFV from Portugal. Previous infection with ASFV OURT88/3 has been shown to confer protection against challenge with related virulent viruses (Boinas et al (2004) J Gen Virol 85:2177-2187; Oura et al (2005) J. Gen. Virol. 86:2445-2450).
It has been demonstrated that CD8+ T cells are required for the protection induced by the OURT88/3 strain, since antibody mediated depletion of CD8+ T cells abrogates protection (Oura et al., 2005, as above).
Studies were carried out using the NIH inbred pig lines cc and dd. In these studies, a control group of 3 dd pigs and a control group of 6 dd pigs were immunised with OURT88/3. In the first of these experiments, following OURT88/3 immunisation one dd pig developed a transient low viremia of log 10 2-3 TCID 50/ml, but no fever or clinical signs of disease. It was observed that 3 of 6 of the cc inbred pigs immunised with OURT88/3 were not protected following lethal challenge with OURT88/3 isolate, whereas protective responses were induced in all dd pigs. These results indicate that the genetic background of the pig influences the response to OURT88/3 inoculation.
In subsequent experiments 5 dd and 5 cc pigs were immunised with OURT88/3 and challenged with OURT88/1 (Takamatsu et al., 2003 unpublished results). This confirmed that protective responses were induced in all dd pigs, but not induced in all cc pigs following immunisation with OURT88/3 and that adverse reactions including transient pyrexia, joint swelling and lameness were induced in some of the cc pigs.
Subsequent experiments were carried out in France using the Anses herd of SPF pigs. In these pigs, similar to observations with cc pigs, some pigs developed adverse reactions including transient fever, joint swelling and lameness following immunisation with OURT88/3 (unpublished results).
Although OURT88/3 has been shown to induce a protective immune response in certain animals, this effect does not appear to be universal. Immunisation with OURT88/3 appears to be ineffective in protecting some pigs from subsequent challenge. It is also associated with the induction of adverse immune responses, such as joint swelling, in some pigs.
There is therefore a need for alternative ASFV vaccine candidates with improved efficacy and safety profiles.